Evolution of the Modern Biosensor

When the term ‘biosensors’ was first coined, they were described to be analytical devices that respond to the concentration of chemical species in biological samples.1 This traditional understanding believed that detection was limited to inorganic compounds, such as metals and gasses. With further research and bioengineering, biosensors are now capable of interacting with small molecules, proteins, viruses, and whole-cells.2-4 Most notable is the exploitation of antibodies in the recognition of biological analytes. In the last 40 years, antibodies have dominated the field of biochemistry and molecular sensors, giving rise to enzyme-linked immunosorbent assay, immunohistochemistry, and flow cytometry.5

Immunosensors are biosensor that uses the antigen-antibody complex to induce a physicochemical change to generate a quantifiable signal.5 Although the specificity conferred by the antigen-antibody interaction is highly attractive, stability of the interaction can be readily compromised by environmental conditions.6 To overcome this limitation, a smaller synthetic derivative of antibodies called Antigen Binding Proteins (ABP) have been engineered.7 ABP is solely comprised of the recombinant binding domains of antibodies, thus circumventing the instability associated with protein folding, and enabling ABP to perform in reducing cellular environments like the bacterial cytoplasm.7

Beyond immunosenors, enzymes are another biosensing platform, popularized by their binding specificity and catalytic activity.8 Macroscopic bioreceptors like organelles, cells and tissue have also been employed to assess biochemical parameters like stress condition, and drug toxicity.9 Presently, one of the most promising biosensing disciplines involve nucleic acids.10 In addition to their roles as storage of genetic information, deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) can serve as the recognition element through hybridization of complementary base pairs, as well as the transducer element through conformation-dependent catalysis.11 Aptamers, DNAzymes, Ribozymes are also nucleic acid molecules that offer unique solutions for recognition and transduction. In the last decade, nucleic acid probes have become increasingly sophisticated through labeling and enzymatic conjugation.12-14 The appeal of nucleic acid biotechnologies lies in its simple, economical and controlled production.12 Moreover, their functionality across a wide range of pH and temperatures make them favorable for field testing.

The discovery of these new and innovative platforms with enhanced sensitivity, selectivity, and portability have arisen to challenge traditional sensors. The modern biosensor is quickly advancing towards inclusive usability and decentralized testing. These disruptive technologies penetrate various industrial sectors that once relied on complex techniques and expensive instrumentation. The success of these newer technologies remains to be seen, nevertheless, the growth of biosensor development over the past 50 years is without a doubt extraordinary.

(1)    Palchetti, I., and Mascini, M. (2010) Biosensor Technology: A Brief History, in Sensors and Microsystems (Malcovati, P., Baschirotto, A., d’Amico, A., and Natale, C., Eds.), pp 15–23. Springer Netherlands.

(2)    Zhou, Q., Son, K., Liu, Y., and Revzin, A. (2015) Biosensors for Cell Analysis. Annu Rev Biomed Eng 17, 165–190.

(3)    Leca‐Bouvier, B., and Blum, L. J. (2005) Biosensors for Protein Detection: A Review. Analytical Letters 38, 1491–1517.

(4)    Nidzworski, D., Pranszke, P., Grudniewska, M., Król, E., and Gromadzka, B. (2014) Universal biosensor for detection of influenza virus. Biosensors and Bioelectronics 59, 239–242.

(5)    Luppa, P. B., Sokoll, L. J., and Chan, D. W. (2001) Immunosensors—principles and applications to clinical chemistry. Clinica Chimica Acta 314, 1–26.

(6)    Chames, P., Van Regenmortel, M., Weiss, E., and Baty, D. (2009) Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157, 220–233.

(7)    Bird, R. E., Hardman, K. D., Jacobson, J. W., Johnson, S., Kaufman, B. M., Lee, S. M., Lee, T., Pope, S. H., Riordan, G. S., and Whitlow, M. (1988) Single-chain antigen-binding proteins. Science 242, 423–426.

(8)    Newman, J. D., and Setford, S. J. Enzymatic biosensors. Mol Biotechnol 32, 249–268.

(9)    De Michele, R., Carimi, F., and Frommer, W. B. (2014) Mitochondrial biosensors. Int. J. Biochem. Cell Biol. 48, 39–44.

(10) Wang, J. (2002) Electrochemical nucleic acid biosensors. Analytica Chimica Acta 469, 63–71.

(11)  Sukhorukov, G. B., Montrel, M. M., Petrov, A. I., Shabarchina, L. I., and Sukhorukov, B. I. (1996) Multilayer films containing immobilized nucleic acids. Their structure and possibilities in biosensor applications. Biosensors and Bioelectronics 11, 913–922.

(12)  Roth, C. M., and Yarmush, M. L. (1999) Nucleic Acid Biotechnology. Annual Review of Biomedical Engineering 1, 265–297.

(13) Tram, K., Kanda, P., Salena, B. J., Huan, S., and Li, Y. (2014) Translating Bacterial Detection by DNAzymes into a Litmus Test. Angew. Chem. Int. Ed. 53, 12799–12802.

(14) Harvey, B., Durrant, I., and Cunningham, M. (1996) The Preparation of Horseradish Peroxidase Labeled Nucleic Acid Probes and Their Detection Using Enhanced Chemiluminescence, in Basic DNA and RNA Protocols (Harwood, A., Ed.), pp 67–75. Humana Press.